Urease is a water soluble enzyme used in dialysis to convert urea into ammonium ions and bicarbonate. Oftentimes, urease can be immobilized electrostatically or covalently on an alumina or silica substrate inside a sorbent cartridge that is designed to be connected to a dialysis system. However, conventional immobilization of urease has been associated with the disadvantages of low loading and leaching of urease that can result in low urease sufficiency in dialysis. Moreover, conventional sorbent dialysis systems cannot, replenish, i.e., provide additional or specified amounts of urease to the sorbent cartridge or dialysis system before, during, or after a dialysis session. The inability to control the amount of urease added or available for system use can be problematic because the amount of urease required for a particular dialysis session can vary. The amount of urease required for a dialysis session may depend on a number of factors such as patient weight, urea load, dialysis time, etc. resulting in different rates and amounts of urease required per session. Using more or less than the required amount of urease for a particular dialysis session can translate into increased expenditures and waste from unused or overused urease as well as other sorbent materials contained in the sorbent cartridge.
Known sorbent dialysis cartridges and systems further cannot measure the amount of urease used during a particular session or replenish or add urease back to the sorbent cartridge or system as needed should a session need additional quantities of urease, or should additional urease be needed in the case of faster fluid flow rates through the sorbent cartridge.
Sometimes, certain sorbent materials such as alumina and zirconium phosphate can be recharged such that the sorbent material is put back into a condition for use in sorbent dialysis. However, known systems cannot recharge some or all of the sorbent materials, some of which can be rechargeable components, within a sorbent cartridge that also contains urease without undesirable effects. For example, recharging zirconium phosphate in the same sorbent cartridge in which urease is immobilized on alumina or silica can result in urease being stripped off the alumina or silica. Known systems cannot therefore replenish urease lost due to the process of recharging zirconium phosphate or other non-water soluble, rechargeable sorbent materials inside the same cartridge, or add a specific amount of urease to a sorbent cartridge or sorbent system.
As such, there is a need for systems, methods, components and devices for optimizing use of sorbent materials such as urease within a sorbent cartridge. The need extends to systems that can replenish urease in a sorbent cartridge and related dialysis systems by either directly adding discrete amounts of urease or by continuously adding urease to the sorbent system by a delivery mechanism. The need includes a sorbent cartridge and related systems in which urease can be added on demand, continuously, and in specified, discrete amounts. The need extends to providing urease at a specified time such as after, before, or during a dialysis session. The need includes providing the urease while the system is operating or off-line. The need includes adding the desired amounts of urease in a simple and convenient manner in adjustable amounts. In general, the need can be broadly described as dynamically adding urease to sorbent cartridges and related dialysis systems. The need can include adjusting the amount of required urease depending on a measured amount of urea detected anywhere in the system or sorbent cartridge or other dialysis parameters.
There is also a need for a mechanism of directly adding urease to a sorbent cartridge, on demand. The need includes a way to inject urease into a sorbent cartridge or a part of a flow path anywhere upstream of the sorbent cartridge in the dialysis system by an easy-to-use delivery mechanism. There is also a need for a sorbent cartridge in which fresh urease can be added via a delivery mechanism to replenish or refill the urease in the sorbent cartridge. There is also a need for measuring an amount of urease required to be dynamically added to a sorbent cartridge depending on a measured amount of urea or a suitable indication of urea conversion known to those of ordinary skill. There is also a need for a sorbent cartridge having a section for containing urease wherein the section can contain an adjustable amount of urease. The need includes a sorbent cartridge optionally having a section for containing one or more sorbent materials in amounts that do not need to be adjusted.
There is a need for a system for adding or replacing urease either directly into the sorbent cartridge or by injecting urease into a delivery mechanism. There is a further need for a closed sorbent cartridge capable of receiving an adjustable amount of urease on demand, and a simple way to measure, replenish and/or refill urease during a dialysis session. The methods and systems require a way for introducing urease in continuous or specified and/or discrete amounts. The methods and systems may involve pre-set amounts of urease or dynamically adjustable amounts of urease. There is also a need for a system capable of replenishing urease that may be stripped out of the sorbent cartridge during maintenance or dialysis session.